Aging enhances vascular dysfunction induced by the Alzheimer's peptide beta-amyloid

Aging is a major risk factor for Alzheimer's disease and the evidence suggests a role for cerebrovascular pathology in cognitive dysfunction. The hypothesis in this study is that aging is a significant risk factor in the effect of the Alzheimer peptide beta-amyloid on endothelium-dependent function of cerebral and peripheral vessels. The diameter response to acetylcholine, an endothelium-dependent vasodilator, was recorded in pressurized segments of rat posterior cerebral vessels from mature (3 months) and aged (20 months) rats. The threshold concentration of beta-amyloid for a significant decrease in the response to acetylcholine was lower in vessels from aged rats (10(-9) M) than in vessels from mature rats (10(-8) M). The threshold concentration of beta-amyloid for a significant decrease in the sensitivity to acetylcholine was lower for ring segments of aorta from aged rats (10(-10) M) than for aorta from mature rats (10(-8) M). Structural changes of the endothelium were first observed in electron micrographs of aorta from aged rats when the concentration of beta-amyloid was 10(-8) M, whereas structural changes in aorta from mature rats did not occur until the concentration of beta-amyloid was increased to 10(-7) M. The results suggest that aging increases the susceptibility of cerebral and peripheral blood vessels to beta-amyloid related dysfunction and that functional change precedes structural change.